The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
Know the risks and potential benefits of clinical studies and talk to your health care provider before participating.
Read our disclaimer for details.

The purpose of this study is to find out the effectiveness of the drug durvalumab (MEDI4736) with or without stereotactic body radiation therapy (SBRT) as treatment for stage I (tumors > 2cm), II, and IIIA non-small cell lung cancer (NSCLC) prior to surgery and one year following surgery.

Condition or disease

Intervention/treatment

Phase

Carcinoma, Non-Small-Cell Lung

Drug: DurvalumabOther: Durvalumab plus SBRT

Phase 2

Detailed Description:

This is a randomized open label phase II trial of preoperative anti-PD-L1 antibody durvalumab with or without concurrent non-ablative radiation followed by surgical resection and postoperative monthly maintenance durvalumab for twelve months.

Disease-free survival [ Time Frame: From date of Durvalumab start date until the date of first documented progression or date of death from any cause, whichever came first, assessed every 6 months for 2 years , then yearly thereafter till year 5. ]

Disease recurrence or death from any cause assessed using history, physical examination and CT scanning, histologically or cytologically confirmed whenever possible.

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Serum bilirubin ≤ 1.5 x institutional upper limit of normal (ULN). This will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician.

Serum creatinine CL>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance:

Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

Women <50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).

Women ≥50 years of age would be considered post-menopausal if they have been amenorrheic exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses >1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).

Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

No prior therapy for their lung cancer.

Exclusion Criteria

Subjects should not enter the study if any of the following exclusion criteria are fulfilled:

Participation in another clinical study with an investigational product during the last 3 weeks.

History of another primary malignancy except for:

Malignancy treated with curative intent and with no known active disease ≥3 years before the first dose of study drug and of low potential risk for recurrence.

Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab, with the exceptions of intranasal,inhaled, topical steroids, or local steroid injections (e.g., intra articular injection), corticosteroids or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid, and steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication).

Any unresolved toxicity (CTCAE grade 2) from therapy for a prior malignancy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.

Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician.

Subjects with irreversible toxicity that is not reasonably expected to be exacerbated by the investigational product may be included (e.g., hearing loss, peripherally neuropathy).

Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.

Female patients who are pregnant or breastfeeding or male or female patients of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab monotherapy.

Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results

Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study.

Receipt of the last dose of therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, or other investigational agent) for an accepted other malignancy as defined in Section 3.3.2 within 30 first dose of study drug for lung cancer.